Variant 19-9857758-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_058164.4(OLFM2):c.317G>A(p.Arg106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,613,768 control chromosomes in the GnomAD database, including 217,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.41 ( 15418 hom., cov: 32)

Exomes 𝑓: 0.52 ( 202473 hom. )

Consequence

OLFM2
NM_058164.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.625

Variant links:

Genes affected

OLFM2 (HGNC:17189): (olfactomedin 2) Involved in positive regulation of smooth muscle cell differentiation. Acts upstream of or within protein secretion. Located in cytoplasm; extracellular region; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

OLFM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.5246563E-4).

BP6

Variant 19-9857758-C-T is Benign according to our data. Variant chr19-9857758-C-T is described in ClinVar as [Benign]. Clinvar id is 1297260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OLFM2	NM_058164.4 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/6	ENST00000264833.9	NP_477512.1
OLFM2	NM_001304347.2 linkuse as main transcript	c.389G>A	p.Arg130Gln	missense_variant	3/6		NP_001291276.1
OLFM2	NM_001304348.2 linkuse as main transcript	c.83G>A	p.Arg28Gln	missense_variant	2/5		NP_001291277.1
OLFM2	XM_047439713.1 linkuse as main transcript	c.113G>A	p.Arg38Gln	missense_variant	3/6		XP_047295669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLFM2	ENST00000264833.9 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/6	1	NM_058164.4	ENSP00000264833

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61784

AN:

151888

Hom.:

15422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.544

Gnomad OTH

AF:

0.424

GnomAD3 exomes

AF:

0.475

AC:

119182

AN:

251110

Hom.:

30986

AF XY:

0.469

AC XY:

63652

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.525

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.554

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.509

GnomAD4 exome

AF:

0.516

AC:

754682

AN:

1461764

Hom.:

202473

Cov.:

AF XY:

0.510

AC XY:

370806

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.0964

Gnomad4 AMR exome

AF:

0.600

Gnomad4 ASJ exome

AF:

0.520

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.560

Gnomad4 NFE exome

AF:

0.550

Gnomad4 OTH exome

AF:

0.480

GnomAD4 genome

AF:

0.406

AC:

61779

AN:

152004

Hom.:

15418

Cov.:

AF XY:

0.406

AC XY:

30132

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.546

Gnomad4 ASJ

AF:

0.532

Gnomad4 EAS

AF:

0.296

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.544

Gnomad4 OTH

AF:

0.421

Alfa

AF:

0.510

Hom.:

45450

Bravo

AF:

0.397

TwinsUK

AF:

0.551

AC:

2044

ALSPAC

AF:

0.553

AC:

2130

ESP6500AA

AF:

0.128

AC:

564

ESP6500EA

AF:

0.549

AC:

4718

ExAC

AF:

0.458

AC:

55603

Asia WGS

AF:

0.304

AC:

1056

AN:

3478

EpiCase

AF:

0.536

EpiControl

AF:

0.534

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 17122126) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;T

Eigen

Benign

0.017

Eigen_PC

Benign

0.031

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.93

D;D;D

MetaRNN

Benign

0.00085

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

N;.;.

MutationTaster

Benign

0.91

P;P

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.12

N;.;.

REVEL

Benign

0.095

Sift

Uncertain

0.015

D;.;.

Sift4G

Benign

0.075

T;T;.

Polyphen

0.94

P;.;.

Vest4

0.050

MPC

0.83

ClinPred

0.018

GERP RS

3.9

Varity_R

0.090

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over